Document Detail


Neisseria meningitidis accelerates ferritin degradation in host epithelial cells to yield an essential iron source.
MedLine Citation:
PMID:  15255894     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In order to colonize humans and cause disease, pathogenic bacteria must assimilate iron from their host. The vast majority of non-haem iron in humans is localized intracellularly, within the storage molecule ferritin. Despite the vast reserves of iron within ferritin, no pathogen has been demonstrated previously to exploit this molecule as an iron source. Here, we show that the Gram-negative diplococcus Neisseria meningitidis can trigger rapid redistribution and degradation of cytosolic ferritin within infected epithelial cells. Indirect immunofluorescence microscopy revealed that cytosolic ferritin is aggregated and recruited to intracellular meningococci (MC). The half-life of ferritin within cultured epithelial cells was found to decrease from 20.1 to 5.3 h upon infection with MC. Supplementation of infected epithelial cells with ascorbic acid abolished ferritin redistribution and degradation and prevented intracellular MC from replicating. The lysosomal protease inhibitor leupeptin slowed ferritin turnover and also retarded MC replication. Our laboratory has shown recently that MC can interfere with transferrin uptake by infected cells (Bonnah R.A., et al., 2000, Cell Microbiol 2: 207-218) and that, perhaps as a result, the infected cells have a transcriptional profile indicative of iron starvation (Bonnah, R.A., et al., 2004, Cell Microbiol 6: 473-484). In view of these findings, we suggest that accelerated ferritin degradation occurs as a response to an iron starvation state induced by MC infection and that ferritin degradation provides intracellular MC with a critical source of iron.
Authors:
Jason A Larson; Heather L Howie; Magdalene So
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular microbiology     Volume:  53     ISSN:  0950-382X     ISO Abbreviation:  Mol. Microbiol.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-16     Completed Date:  2004-10-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8712028     Medline TA:  Mol Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  807-20     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Blackwell Publishing Ltd
Affiliation:
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA. larsonja@ohsu.edu
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MeSH Terms
Descriptor/Qualifier:
Cell Division
Cell Line
Cervix Uteri / cytology
Chromatography, Gel
Epithelial Cells / microbiology*,  physiology
Female
Ferritins / genetics*,  metabolism*
Half-Life
Humans
Iron / metabolism*
Neisseria meningitidis / metabolism*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
AI32493/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 7439-89-6/Iron; 9007-73-2/Ferritins

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